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Epidemic of global obesity causes many problems to contemporary medicine. One of them is increased risk of cancers, especially relationship between obesity and HCC (hepatocellular carcinoma). A team of researchers under the guidance of M. Hassan conducted a wide retrospective study on an association between obesity in early adulthood and HCC. Results were published in American Gastroenterology Journal.
The study involved 622 American patients with newly diagnosed HCC and a control group of 660 healthy individuals who were unrelated to the patients. Both groups were matched according to age, sex and place of residence. They were questioned about changes of their body mass during their lifetime and exposure to many HCC risk factors, such as infection with hepatotropic viruses, smoking, alcohol consumption, diabetes mellitus, family history etc.
Obesity (BMI >30 kg/m²) in early adulthood (between mid-20s and mid-40s) was significantly more often in group diagnosed with HCC than in the control one. The risk of HCC development was higher even when obesity was not accompanied by other risk factors. Moreover, the higher BMI between 20s and 40s, the earlier the onset of the disease (nearly 4 months earlier for every 1 BMI unit on average). On the other hand, obesity did not seem to influence the clinical features of the tumor (such as vascular invasion, portal thrombosis, extrahepatic metastasis, lymph node involvement, tumor differentiation etc.). Additionally, previous studies have shown no negative correlation between obesity and surgical hepatectomy outcome in HCC.
Pathophysiology of HCC development due to obesity includes a few mechanisms. Obesity causes chronic moderate inflammatory reaction and activation of many proinflammatory cytokines and adipokines. It results in a sequence: insulin resistance – hepatic steatosis – NAFLD (non-alcoholic fatty liver disease) – NASH (non-alcoholic steatohepatitis) – fibrosis – cirrhosis – cancer.
DNA of hepatocytes may be destroyed directly by ROS and RNS (reactive oxygen and nitrogen species).
Recently, a role of gut microbiota in liver inflammatory processes is being more emphasized. Changes in gut microbiota (for example due to inappropriate diet) cause activation of immunity system thus fostering chronic liver inflammation and NAFLD.
To sum up, Hassan’s et al. study confirms the association of obesity between mid-20s and mid-40s and HCC occurrence. Both, obesity as an independent factor and coexisting with other environmental and lifestyle risk factors. As the problem of obesity is getting global, there is a need for further research to prevent HCC development in patients with metabolic syndrome, diabetes mellitus and NAFLD. So far, it is known that metformin and coffee consumption have positive influence and further studies may help to develop other agents which will be more effective.
Written by: Maja Mirska
Source:
1. Hassan MM, Abdel-Wahab R, Kaseb A, et al. Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma. Gastroenterology 2015; 149:119–129.
2. Sun B, Karin M. Obesity, inflammation, and liver cancer. Journal of Hepatology 2012; 56:704–713.
3. Kew MC. Obesity as a cause of hepatocellular carcinoma. Annals of Hepatology 2015; 14 (3): 209-303.
4. Farrell G. Insulin Resistance, Obesity, and Liver Cancer. International Digestive Disease Forum, Hong Kong, 2013. Clinical Gastroenterology and Hepatology 2014;12:117–119.
5. Guo Z, JunZhang, Jing-Hang Jiang, Le-Qun Li, Bang-De Xiang. Obesity Does Not Influence Outcomes in Hepatocellular Carcinoma Patients following Curative Hepatectomy. PLOS ONE | DOI:10.1371/journal.pone.0125649 May 12, 2015.
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